PCDH19 Gene Mutations In Three Patients With Epilepsy And Clinical Analysis

ObjectiveIn the present study,we assessed mutations in the PCDH19 gene and the clinical features of a group of three patients with early infantile epileptic encephalopathy and aimed to provide further insight into the understanding of epilepsy and mental retardation limited to females(EFMR;MIM 300088).MethodsTwo millilitres of venous blood was collected from each patient and each parent of the subject for gene testing: including nervous system diseases “big bag”,epilepsy and related paroxysmal diseases.Candidate genes were screened for mutations associated with nervous system diseases in the coding exons and intron–exon boundaries using PCR of genomic DNA followed by sequencing.The variations were sequenced with next-generation sequencing and verified with first-generation sequencing.Results We described three variations in the PCDH19 gene in patients with epilepsy who developed generalized seizures occurring in clusters with or without triggering by fever.Exome sequencing of a multigene epilepsy panel revealed three mutations in the PCDH19 gene in a mosaic male and two unrelated females.These included a frameshift mutation c.1508?1509insT(p.Thr504HisfsTer19),a missense mutation c.1681 C > T(p.Pro561Ser)and a nonsense mutation c.918 C > G(p.Tyr306Ter).Of the three mutations in the PCDH19 gene,the frameshift variation in a mosaic male is novel and de novo,the missense variation is de novo and is the second ever reported in females,and the nonsense variation was inherited from the paternal line and is the first example discovered in a female.Conclusions1.Our study provides new insight into and perspectives for the molecular genetic link between epilepsy and PCDH19 alterations.2.Our new findings of the male mosaic variant broaden the spectrum of PCDH19-related epilepsy and provide a new understanding of this complex genetic disorder.3.Our study found that the clinical phenotype spectrum of PCDH19 gene-related epilepsy is broad,and the characteristics of cluster seizures are the most prominent.